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Browsing by Author "Vuppalanchi, Raj"
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Item A composite score using quantitative magnetic resonance cholangiopancreatography predicts clinical outcomes in primary sclerosing cholangitis(Elsevier, 2023-06-29) Vuppalanchi, Raj; Are, Vijay; Telford, Alison; Young, Liam; Mouchti, Sofia; Ferreira, Carlos; Kettler, Carla; Gromski, Mark; Akisik, Fatih; Chalasani, Naga; Radiology and Imaging Sciences, School of MedicineBackground & aims: Magnetic resonance cholangiopancreatography (MRCP) for evaluation of biliary disease currently relies on subjective assessment with limited prognostic value because of the lack of quantitative metrics. Artificial intelligence-enabled quantitative MRCP (MRCP+) is a novel technique that segments biliary anatomy and provides quantitative biliary tree metrics. This study investigated the utility of MRCP+ as a prognostic tool for the prediction of clinical outcomes in primary sclerosing cholangitis (PSC). Methods: MRCP images of patients with PSC were post-processed using MRCP+ software. The duration between the MRCP and clinical event (liver transplantation or death) was calculated. Survival analysis and stepwise Cox regression were performed to investigate the optimal combination of MRCP+ metrics for the prediction of clinical outcomes. The resulting risk score was validated in a separate validation cohort and compared with an existing prognostic score (Mayo risk score). Results: In this retrospective study, 102 patients were included in a training cohort and a separate 50 patients formed a validation cohort. Between the two cohorts, 34 patients developed clinical outcomes over a median duration of 3 years (23 liver transplantations and 11 deaths). The proportion of bile ducts with diameter 3-5 mm, total bilirubin, and aspartate aminotransferase were independently associated with transplant-free survival. Combined as a risk score, the overall discriminative performance of the MRCP+ risk score (M+BA) was excellent; area under the receiver operator curve 0.86 (95% CI: 0.77, 0.95) at predicting clinical outcomes in the validation cohort with a hazard ratio 5.8 (95% CI: 1.5, 22.1). This was superior to the Mayo risk score. Conclusions: A composite score combining MRCP+ with total bilirubin and aspartate aminotransferase (M+BA) identified PSC patients at high risk of liver transplantation or death. Prospective studies are warranted to evaluate the clinical utility of this novel prognostic tool. Impact and implications: Primary sclerosis cholangitis (PSC) is a disease of the biliary tree where inflammation and fibrosis cause areas of narrowing (strictures) and expansion (dilatations) within the biliary ducts leading to liver failure and/or cancer (cholangiocarcinoma). In this study, we demonstrate that quantitative assessment of the biliary tree can better identify patients with PSC who are at high risk of either death or liver transplantation than a current blood-based risk score (Mayo risk score).Item Application of the Latest Advances in Evidence-Based Medicine in Primary Biliary Cholangitis(Wolters Kluwer, 2023) Kowdley, Kris V.; Bowlus, Christopher L.; Levy, Cynthia; Mayo, Marlyn J.; Pratt, Daniel S.; Vuppalanchi, Raj; Younossi, Zobair M.; Medicine, School of MedicinePrimary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune liver disease that can progress to end-stage liver disease and its complications. A previous expert review panel collaborated on a consensus document for gastroenterologists and other healthcare professionals regarding the care of patients with PBC. Subsequently, there have been several recent important developments in the diagnosis, treatment, and monitoring of patients with PBC. These include updates to prognostic models on risk stratification, new noninvasive tools for staging of disease, updates to the appropriate use of and long-term treatment results with obeticholic acid as a second-line treatment, the emerging therapeutic role of fibrates, and the advancement of investigational agents for managing PBC. In this updated expert consensus document, we provide updates on staging, the use of noninvasive prognostic tools, and a treatment algorithm to provide evidence-based and practical tools for clinicians who manage PBC, with the ultimate goal to improve the long-term outcomes for patients with this chronic liver disease.Item Assessment and management of comorbidities (including cardiovascular disease) in patients with nonalcoholic fatty liver disease(Wiley, 2012-09-25) Corey, Kathleen E.; Vuppalanchi, Raj; Medicine, School of MedicineNonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. Nonalcoholic steatohepatitis, the progressive form of NAFLD, can lead to end‐stage liver disease and hepatocellular carcinoma. However, the consequences of NAFLD are not confined to the liver. NAFLD is associated with an increased risk of cardiovascular disease (CVD) and is frequently associated with metabolic syndrome. Thus, there is a pressing need for the diagnosis and management of the comorbidities of NAFLD, including CVD. This review will guide clinicians in the assessment and management of metabolic disease and CVD in patients with NAFLD.Item Attendance at a Transitional Liver Clinic May Be Associated with Reduced Readmissions for Patients with Liver Disease(Elsevier, 2022) Yoder, Lindsay; Mladenovic, Andrea; Pike, Francis; Vuppalanchi, Raj; Hanson, Haleigh; Corbito, Laura; Desai, Archita P.; Chalasani, Naga; Orman, Eric S.; Medicine, School of MedicineIntroduction: Patients with liver disease have high rates of early hospital readmission, but there are no studies of effective, scalable interventions to reduce this risk. In this study, we examined the impact of a Physician Assistant (PA)-led post-discharge Transitional Liver Clinic (TLC) on hospital readmissions. Methods: We performed a cohort study of all adults seen by a hepatologist during admission to a tertiary care center in 2019 (excluding transplant patients). We compared those who attended the TLC with those who did not, with respect to 30-day readmission and mortality. Propensity score-adjusted modeling was used to control for confounding. Results: Of 498 patients, 98 were seen in the TLC; 35% had alcoholic liver disease and 58% had cirrhosis. Attendees were similar to non-attendees with respect to demographics, liver disease characteristics and severity, comorbidities, and discharge disposition. Thirty-day cumulative incidence of readmissions was 12% in TLC attendees, compared with 22% in non-attendees (P = .02), while 30-day mortality was similar (2.0% vs 4.3%; P = .29). In a model using propensity score adjustment, TLC attendance remained associated with reduced readmissions (subhazard ratio 0.52; 95% confidence interval, 0.27-0.997; P = .049). The effect of TLC was greater in women compared with men (P = .07) and in those without chronic kidney disease (P = .02), but there were no differences across other subgroups. Conclusions: Patients with liver disease seen in a PA-led TLC may have a significant reduction in the 30-day readmission rate. Randomized trials are needed to establish the efficacy of PA-led post-discharge transitional care for this population.Item Behaviors, symptoms, and outcomes of North American patients with autoimmune hepatitis during the COVID-19 pandemic(BMJ, 2021-12) Vuppalanchi, Vahin; Gelow, Kayla; Vuppalanchi, Raj; Lammert, Craig; Green, Kelsey; Medicine, School of MedicineThe management of patients with autoimmune hepatitis (AIH) in the era of SARS-CoV-2 is challenging given minimal published clinical data. We used a large cohort of patients with AIH across the USA to investigate the differences in known risk factors for severe SARS-CoV-2 and AIH characteristics among patients who experienced symptoms consistent with COVID-19 illness versus those who did not. Additionally, we explored the effect of living through the SARS-CoV-2 pandemic on the extrahepatic symptoms and behaviors of patients with AIH. An invitation to complete a COVID-19-specific questionnaire was publicized in well-established social media cohorts of patients with AIH. Eligibility criteria were age ≥18 years, US residency, and an AIH diagnosis by a physician. A total of 420 individuals were eligible for the study. Symptoms consistent with COVID-19 were reported in 11% (n=48) with 3 patients requiring hospitalizations. Body mass index (BMI) >40 kg/m2 (23% vs 10%, p=0.01) and exposure to house (33% vs 3%, p=0.0001) or work (38% vs 17%, p=0.02) contacts with COVID-19 were factors found higher in those with symptoms. Cirrhosis or steroid use or immunosuppression was not significantly different between symptomatic and non-symptomatic groups. Worsening fatigue (45% vs 30%, p=0.06), anxiety (89% vs 70%, p=0.08), and itch (40% vs 18%, p=0.03) were more common among those reporting COVID-19 symptoms compared with those without. BMI >40 kg/m2 and exposure to contacts with COVID-19 illness but not cirrhosis or immunosuppression were associated with increased risk of COVID-19 illness in patients with AIH.Item Cannabidiol (CBD) Consumption and Perceived Impact on Extrahepatic Symptoms in Patients with Autoimmune Hepatitis(Springer, 2019-07-30) Mathur, Karan; Vuppalanchi, Vahin; Gelow, Kayla; Vuppalanchi, Raj; Lammert, Craig; Medicine, School of MedicineBackground and Aims Utilization and safety of cannabidiol (CBD) in patients with autoimmune hepatitis (AIH) are currently unknown. We aimed to identify the frequency of CBD use, impact on symptoms, and safety profile. Methods An invitation to complete a CBD-specific questionnaire was posted every other day to well-established autoimmune hepatitis Facebook communities (combined membership of 2600 individuals) during a 10-day study period. Age ≥ 18 years and an AIH diagnosis by a physician were the eligibility criteria for participation in the survey. Results In total, 371 AIH patients (median age 49 years, 32% reported advanced fibrosis) completed the questionnaire. Respondents were 91% women, 89% Caucasian, and 89% from North America. Ninety-three (25%) respondents were ever CBD users, with 55 of them (15% of the survey responders) identified as current users. Among ever users, 45.7% reported their treating doctors were aware of their CBD use. The most common reason cited for CBD use was pain (68%), poor sleep (62%), and fatigue (38%). Most respondents using CBD for these symptoms reported a significant improvement in pain (82%), sleep (87%), and fatigue (61%). In ever CBD users, 17.3% were able to stop a prescription medication because of CBD use: pain medication (47%), immunosuppression (24%), and sleep aids (12%). Side effects attributed to CBD use were reported in 3% of CBD users, yet there were no reported emergency department visits or hospitalizations. Conclusion CBD use was not uncommon in patients with AIH, and its use was associated with reports of improvement in extrahepatic symptoms.Item Cholestasis in the First Trimester Associated with Rare ABCG5/8 Variants: A Case Study(2022-07-28) Ganapaneni, Sruthi; Arul Dhas, Blessed Winston; Vuppalanchi, Raj; Quinney, SaraCholestasis in the First Trimester Associated with Rare ABCG5/8 Variants: A Case Study Sruthi Ganapaneni 1, Blessed Winston Arul Dhas 2, Raj Vuppalanchi 2, Sara Quinney 2,3 1 Indiana University School of Medicine; 2 Indiana University School of Medicine, Department of Medicine; 3 Indiana University School of Medicine, Department of Obstetrics and Gynecology Purpose/Background: Obstetric cholestasis, or intrahepatic cholestasis of pregnancy (ICP), is a liver disease that usually presents in the third trimester of pregnancy. It is characterized by pruritis that is associated with elevated liver enzymes and bile acids. This condition can have potentially serious effects on the fetus due to the buildup of serum bile acids resulting from the obstruction of bile flow. Methods/Case Overview: A 28-year-old patient, who was pregnant for the third time, developed pruritis in the first trimester and presented with blood work that showed elevated total bile acids and liver enzymes. A medical history revealed similar symptoms amongst her female relatives during their pregnancies as well as the patient’s own previous pregnancies, suggesting a genetic component in the etiology of the disease. Genetic testing supported this hypothesis and showed variants of unknown significance that indicated a duplication in the ABCG5 and ABCDG8 genes. Results/Discussion: This finding was rather unusual as these genes have not yet been clinically associated with ICP. The ABCG5 and ABCG8 genes code for canicular bile transporters in the liver that transport cholesterol into the bile. Overexpression of these transporters due to the duplication in her genes may result in increased transport of cholesterol into bile, disrupting the regular composition of bile. The resulting increased bile viscosity may cause bile stasis or blockage, and this proposed mechanism can possibly explain the pathophysiology behind this unusual case of cholestasis. Conclusion and Potential Impact: ICP can have potential serious effects on the developing fetus, and its etiology is still being understood. The novel ABCG5/8 gene duplication is a novel variant that may lead to earlier onset of ICP than commonly known variants.Item Circulating cell-free messenger RNA secretome characterization of primary sclerosing cholangitis(Wolters Kluwer, 2023-05-23) Chalasan, Naga; Vuppalanchi, Raj; Lammert, Craig; Gawrieh, Samer; Braun, Jerome V.; Zhuang, Jiali; Ibarra, Arkaitz; Ross, David A.; Nerenberg, Michael; Quake, Stephen R.; Sninsky, John J.; Toden, Shusuke; Medicine, School of MedicineBackground: Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by multifocal bile duct strictures. To date, underlying molecular mechanisms of PSC remain unclear, and therapeutic options are limited. Methods: We performed cell-free messenger RNA (cf-mRNA) sequencing to characterize the circulating transcriptome of PSC and noninvasively investigate potentially bioactive signals that are associated with PSC. Serum cf-mRNA profiles were compared among 50 individuals with PSC, 20 healthy controls, and 235 individuals with NAFLD. Tissue and cell type-of-origin genes that are dysregulated in subjects with PSC were evaluated. Subsequently, diagnostic classifiers were developed using PSC dysregulated cf-mRNA genes. Results: Differential expression analysis of the cf-mRNA transcriptomes of PSC and healthy controls resulted in identification of 1407 dysregulated genes. Furthermore, differentially expressed genes between PSC and healthy controls or NAFLD shared common genes known to be involved in liver pathophysiology. In particular, genes from liver- and specific cell type-origin, including hepatocyte, HSCs, and KCs, were highly abundant in cf-mRNA of subjects with PSC. Gene cluster analysis revealed that liver-specific genes dysregulated in PSC form a distinct cluster, which corresponded to a subset of the PSC subject population. Finally, we developed a cf-mRNA diagnostic classifier using liver-specific genes that discriminated PSC from healthy control subjects using gene transcripts of liver origin. Conclusions: Blood-based whole-transcriptome cf-mRNA profiling revealed high abundance of liver-specific genes in sera of subjects with PSC, which may be used to diagnose patients with PSC. We identified several unique cf-mRNA profiles of subjects with PSC. These findings may also have utility for noninvasive molecular stratification of subjects with PSC for pharmacotherapy safety and response studies.Item Clinical and histologic features of azithromycin-induced liver injury(Elsevier, 2015-02) Martinez, Melissa A.; Vuppalanchi, Raj; Fontana, Robert J.; Stolz, Andrew; Kleiner, David E.; Hayashi, Paul H.; Gu, Jiezhun; Hoofnagle, Jay H.; Chalasani, Naga; Department of Medicine, IU School of MedicineBACKGROUND & AIMS: Rare cases of azithromycin-induced hepatotoxicity have been reported, with variable clinical and histologic features. We characterized clinical features and outcomes of azithromycin-induced liver injury. METHODS: We identified patients with azithromycin-induced liver injury from the Drug-Induced Liver Injury Network Prospective Study who had causality scores of definite, highly likely, or probable. Demographic, clinical, and laboratory data and 6-month outcomes were examined. RESULTS: Eighteen patients (72% female; mean age, 37 y) had causality scores of definite (n = 1), highly likely (n = 9), or probable (n = 8). Common presenting symptoms were jaundice, abdominal pain, nausea, and/or pruritus. For 16 patients, abnormal results from liver tests were first detected 14 days after azithromycin cessation (range, 9-20 d). The median duration of azithromycin treatment was 4 days (range, 2-7 d). The pattern of injury was hepatocellular in 10 patients, cholestatic in 6 patients, and mixed in 2 patients. The mean peak level of alanine aminotransferase was 2127 IU/L, of alkaline phosphatase was 481 IU/L, and of total bilirubin was 9.2 mg/dL. Liver histology showed ductopenia and veno-occlusive changes in a few patients. Two individuals had severe hypersensitivity cutaneous reactions. After 6 months, 8 patients had recovered, 4 patients had chronic injury, 1 patient died, and 1 patient underwent liver transplantation (outcomes were unavailable for 4 patients). Two of the patients who died or underwent liver transplantation had underlying chronic liver disease. CONCLUSIONS: Azithromycin-induced liver injury occurs within 1 to 3 weeks after azithromycin initiation and predominantly is hepatocellular in nature. Although most patients recover fully, severe cutaneous reactions, chronic injury, and serious complications leading to death or liver transplantation can occur (ClinicalTrials.gov identifier, NCT00345930).Item Clinical Characteristics and HLA Associations of Azithromycin-Induced Liver Injury(Wiley, 2024) Conlon, Caroline; Li, Yi-Ju; Ahmad, Jawad; Barnhart, Huiman; Fontana, Robert J.; Ghabril, Marwan; Hayashi, Paul H.; Kleiner, David E.; Lee, William M.; Navarro, Victor; Odin, Joseph A.; Phillips, Elizabeth J.; Stolz, Andrew; Vuppalanchi, Raj; Halegoua-DeMarzio, Dina; Drug-Induced Liver Injury Network (DILIN); Medicine, School of MedicineBackground: Azithromycin (AZ) is a widely used antibiotic. The aim of this study was to characterise the clinical features, outcomes, and HLA association in patients with drug-induced liver injury (DILI) due to AZ. Methods: The clinical characteristics of individuals with definite, highly likely, or probable AZ-DILI enrolled in the US Drug-Induced Liver Injury Network (DILIN) were reviewed. HLA typing was performed using an Illumina MiSeq platform. The allele frequency (AF) of AZ-DILI cases was compared to population controls, other DILI cases, and other antibiotic-associated DILI cases. Results: Thirty cases (4 definite, 14 highly likely, 12 probable) of AZ-DILI were enrolled between 2004 and 2022 with a median age of 46 years, 83% white, and 60% female. Median duration of AZ treatment was 5 days. Latency was 18.5 days. 73% were jaundiced at presentation. The injury pattern was hepatocellular in 60%, cholestatic in 27%, and mixed in 3%. Ten cases (33%) were severe or fatal; 90% of these were hepatocellular. Two patients required liver transplantation. One patient with chronic liver disease died of hepatic failure. Chronic liver injury developed in 17%, of which 80% had hepatocellular injury at onset. HLA-DQA1*03:01 was significantly more common in AZ-DILI versus population controls and amoxicillin-clavulanate DILI cases (AF: 0.29 vs. 0.11, p = 0.001 and 0.002, respectively). Conclusion: Azithromycin therapy can lead to rapid onset of severe hepatic morbidity and mortality in adult and paediatric populations. Hepatocellular injury and younger age were associated with worse outcomes. HLA-DQA1*03:01 was significantly more common in AZ cases compared to controls.